A lead = a precise mechanistic hypothesis on a bacterial defense family, with explicit falsifiability criteria, signed by DID, evaluable by peers. Lead content is currently in French (translation pending). Source content visible below.
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Bacterial retrons produce a chimeric RNA/DNA molecule (mssDNA) via their endogenous reverse transcriptase (RT). This mssDNA acts as a molecular decoy or sensor of phage infection, triggering downstream effector systems. Retron RT is phyloge…
2 targets
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Druantia encodes MotA, an ATPase of the AAA⁺ superfamily, which monitors DNA replication integrity during phage infection. AAA⁺ ATPases are among the most conserved proteins in evolution and include major eukaryotic antiviral actors (VPS4 i…
1 target
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Lamassu is an anti-phage defense system that depletes specific nucleotide pools upon infection, starving the phage of substrates essential for genome replication. By mapping the substrate specificity of Lamassu NTPases and comparing it to t…
2 targets
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Hachiman is a two-component anti-phage defense system (HamA ATPase + HamB effector) noted for its unusually broad antiviral activity across phage taxonomic groups. This breadth suggests recognition of a conserved phage feature — potentially…
2 targets
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ThsB, the TIR sensor of the Thoeris system, hydrolyzes NAD⁺ upon phage infection — the same mechanism as human SARM1, the only TIR-domain NAD⁺-hydrolase in vertebrates. Using ThsB as an evolutionary template to identify allosteric modulator…
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The bacterial RADAR complex (RdrA ATPase + RdrB deaminase) edits double-stranded RNA A→I, in direct functional homology with human ADAR1/ADAR2. Identify allosteric modulators of RdrB by in silico screening and test their transfer to ADAR1 —…
3 targets
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Pycsar synthesizes cyclic pyrimidine signals (cCMP, cUMP) unknown to human immunity. Design analogues stabilized against endogenous phosphodiesterases to selectively activate TLRs/interferon pathways without affecting cGAS-STING — a second …
3 targets
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Bacterial Schlafen cleave cellular tRNAs to block the translation of viral proteins (perfect functional homology with human SLFN11). Use their compact catalytic architecture as a template to screen for selective allosteric modulators of SLF…
2 targets
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Bacterial viperins (Pfam Radical_SAM) convert CTP/UTP/GTP into 3'-dehydro analogues (ddhNTPs). Viral RdRps incorporate these as chain terminators. Chemically enumerate ddhNTP derivatives and their prodrugs to cross the membrane of eukaryoti…
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Design phosphorothioate analogues of cGAMP/c-di-AMP that bind to CBASS effectors (Cap4, NucC) without triggering their enzymatic activation, acting as competitive allosteric inhibitors.…
2 targets
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